CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

Martin Franke, Elisa De la Calle-Mustienes, Ana Neto, María Almuedo-Castillo, Ibai Irastorza-Azcarate, Rafael D. Acemel, Juan J. Tena, José M. Santos-Pereira () and José L. Gómez-Skarmeta
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Martin Franke: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide
Elisa De la Calle-Mustienes: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide
Ana Neto: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide
María Almuedo-Castillo: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide
Ibai Irastorza-Azcarate: Max-Delbrück Center for Molecular Medicine
Rafael D. Acemel: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide
Juan J. Tena: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide
José M. Santos-Pereira: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide
José L. Gómez-Skarmeta: Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes.

Date: 2021
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DOI: 10.1038/s41467-021-25604-5

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